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Rong, Z. ; Mai, H. ; Ebert, G. ; Kapoor, S. ; Puelles, V.G.* ; Czogalla, J.* ; Hu, S.* ; Su, J. ; Prtvar, D.* ; Singh, I. ; Schädler, J.* ; Delbridge, C.* ; Steinke, H.* ; Frenzel, H.* ; Schmidt, K.* ; Braun, C.* ; Bruch, G.* ; Ruf, V.* ; Ali, M. ; Sühs, K.W.* ; Nemati, M.* ; Hopfner, F.* ; Ulukaya, S. ; Jeridi, D. ; Mistretta, D. ; Caliskan, Ö.S. ; Wettengel, J.M. ; Cherif, F.* ; Kolabas, Z.I. ; Molbay, M. ; Horvath, I. ; Zhao, S. ; Krahmer, N. ; Yildirim, A.Ö. ; Ussar, S. ; Herms, J.* ; Huber, T.B.* ; Tahirovic, S.* ; Schwarzmaier, S.M.* ; Plesnila, N.* ; Höglinger, G.* ; Ondruschka, B.* ; Bechmann, I.* ; Protzer, U. ; Elsner, M. ; Bhatia, H.S. ; Hellal, F. ; Ertürk, A.

Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19.

Cell Host Microbe 32, 2112-2130.e10 (2024)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
SARS-CoV-2 infection is associated with long-lasting neurological symptoms, although the underlying mechanisms remain unclear. Using optical clearing and imaging, we observed the accumulation of SARS-CoV-2 spike protein in the skull-meninges-brain axis of human COVID-19 patients, persisting long after viral clearance. Further, biomarkers of neurodegeneration were elevated in the cerebrospinal fluid from long COVID patients, and proteomic analysis of human skull, meninges, and brain samples revealed dysregulated inflammatory pathways and neurodegeneration-associated changes. Similar distribution patterns of the spike protein were observed in SARS-CoV-2-infected mice. Injection of spike protein alone was sufficient to induce neuroinflammation, proteome changes in the skull-meninges-brain axis, anxiety-like behavior, and exacerbated outcomes in mouse models of stroke and traumatic brain injury. Vaccination reduced but did not eliminate spike protein accumulation after infection in mice. Our findings suggest persistent spike protein at the brain borders may contribute to lasting neurological sequelae of COVID-19.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Sars-cov-2 ; Brain ; Long Covid ; Mrna Vaccine ; Meninges ; Neurodegeneration ; Neuroinflammation ; Skull ; Spike Protein ; Tissue Clearing; Neutrophil Extracellular Traps; Controlled Cortical Impact; Ischemic-stroke; Coronavirus; Craniotomy; Proteomics; Receptor; Injury; Route; Cells
ISSN (print) / ISBN 1931-3128
e-ISSN 1934-6069
Zeitschrift Cell Host & Microbe
Quellenangaben Band: 32, Heft: 12, Seiten: 2112-2130.e10 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Tissue Engineering and Regenerative Medicine (ITERM)
Institute of Virology (VIRO)
Institute of Diabetes and Obesity (IDO)
Institute of Lung Health and Immunity (LHI)
Förderungen European Research Council Consolidator grant
NOMIS Hu-man Heart Atlas Project grant (Nomis Foundation)
Vascular Dementia Research Foundation
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy within the frame-work of the Munich Cluster for Systems Neurology
German Federal Ministry of Education and Research
(BMBF)
DFG
State of Bavaria
European Union
Helmholtz Association's Initiative and Networking Fund
GoBio project

China Scholarship Council (CSC)